An information theoretic thresholding method for detecting protein colocalizations in stacks of fluorescence images

Barysenka, Andrei; Dress, Andreas; Schubert, Walter

doi:10.1016/j.jbiotec.2010.01.009

Cited by 17 publications

(7 citation statements)

References 18 publications

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“…The corresponding medical indication should be made as early as possible to prevent irreversible damage of the motor system. The MUSIC robotics technology and corresponding protocols have been described in detail [18]- [24]. The experiences reported here might stimulate a systematic mathematical approach to the molecular geometry of emergence mechanisms in diseases, which cannot be revealed by large scale expression profiling without anatomical resolution, as illustrated in Figure 2, on the right.…”

Section: Discussionmentioning

confidence: 96%

A Platform for Parameter Unlimited Molecular Geometry Imaging Obviously Enabling Life Saving Measures in ALS

Schubert¹

2018

APM

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This article deals with a molecular geometry imaging platform capable of mapping the spatial protein-colocalisation and anti-colocalisation code of large molecular systems at a time. The platform called molecular unlimited systems imaging cycler (MUSIC) robotics was applied to amyotrophic lateral sclerosis (ALS). The detection of ALS specific cells with a corresponding multimolecular geometry in the blood led to therapeutic depletion of these cells and to recovery of the treated patient, obviously because this therapy interferes with pathogenic invasion of these cells into the central nervous system, where they axotomize motor axons. Large scale geometry MUSIC robotics imaging of up to 4.5 × 10 481 power of combinatorial molecular resolution is key to detect these cells and to control depletion therapy for clinical success. These data and new possibilities may argue for clinical application and for a systematic research in the field of molecular geometry of diseases to discover new mathematically defined insight.

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Section: Discussionmentioning

confidence: 96%

A Platform for Parameter Unlimited Molecular Geometry Imaging Obviously Enabling Life Saving Measures in ALS

Schubert¹

2018

APM

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“…1(c) by exemplifying the first fluorescence signals obtained in one optical plane out of 20 imaged in z-direction of the tissue in 200 nm steps (see below). This was followed by a binarization step displaying each signal as absent or present (0/1) by using an expert-based 25 and automated approach for threshold detection 44 45 ( Fig. 5b ).…”

Section: Methodsmentioning

confidence: 99%

Large molecular systems landscape uncovers T cell trapping in human skin cancer

Hillert¹,

Gieseler

Krusche³

et al. 2016

Sci Rep

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Immune surveillance of tumour cells is an important function of CD8 T lymphocytes, which has failed in cancer for reasons still unknown in many respect but mainly related to cellular processes in the tumour microenvironment. Applying imaging cycler microscopy to analyse the immune contexture in a human skin cancer we could identify and map 7,000 distinct cell surface-associated multi-protein assemblies. The resulting combinatorial geometry-based high-functional resolution led to discovery of a mechanism of T cell trapping in the epidermis, which involves SPIKE, a network of suprabasal keratinocyte projections piercing and interconnecting CD8 T cells. It appears initiated by clusters of infrabasal T and dendritic cells connected via cell projections across a fractured basal lamina to suprabasal keratinocytes and T lymphocytes.

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“…Imaging cycler microscopy based discovery of molecular networks in situ 4 . (a) Direct realtime protein profiling in 100-dimensional ICM data set using an algorithm based on the similarity mapping approach 19 , 20 , 22 . Each data point has a PCMD of 256 100 .…”

Section: Icroscopic M Ethod Fmentioning

confidence: 99%

Advances in toponomics drug discovery: Imaging cycler microscopy correctly predicts a therapy method of amyotrophic lateral sclerosis

Schubert

2015

Cytometry Pt A

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An imaging cycler microscope (ICM) is a fully automated (epi)fluorescence microscope which overcomes the spectral resolution limit resulting in parameter-and dimensionunlimited fluorescence imaging. This enables the spatial resolution of large molecular systems with their emergent topological properties (toponome) in morphologically intact cells and tissues displaying thousands of multi protein assemblies at a time. The resulting combinatorial geometry of these systems has been shown to be key for invivo/in-situ detection of lead proteins controlling protein network topology and (dys)-function: If lead proteins are blocked or downregulated the corresponding disease protein network disassembles. Here, correct therapeutic predictions are exemplified for ALS. ICM drug target studies have discovered an 18-dimensional cell surface molecular system in ALS-PBMC with a lead drug target protein, whose therapeutic downregulation is now reported to show statistically significant effect with stop of disease progression in one third of the ALS patients. Together, this clinical and the earlier experimental validations of the ICM approach indicate that ICM readily discovers in vivo robustness nodes of disease with lead proteins controlling them. Breaking in vivo robustness nodes using drugs against their lead proteins is likely to overcome current high drug attrition rates. V C 2015 The Author. Published by Wiley Periodicals, Inc, on behalf of ISAC.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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An information theoretic thresholding method for detecting protein colocalizations in stacks of fluorescence images

Cited by 17 publications

References 18 publications

A Platform for Parameter Unlimited Molecular Geometry Imaging Obviously Enabling Life Saving Measures in ALS

A Platform for Parameter Unlimited Molecular Geometry Imaging Obviously Enabling Life Saving Measures in ALS

Large molecular systems landscape uncovers T cell trapping in human skin cancer

Advances in toponomics drug discovery: Imaging cycler microscopy correctly predicts a therapy method of amyotrophic lateral sclerosis

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